Carcinogenicity studies of astemizole in mice and rats.

The histamine H1 antagonist astemizole (Hismanal) was tested for carcinogenicity in Swiss mice and Wistar rats. Astemizole was administered with the food to mice for 18 and to rats for 24 consecutive months. The doses given--approximately 5, 20, and 80 mg/kg body weight.day--were equivalent to 25, 100, and 400 times, respectively, the recommended human dose of 10 mg/day. Survival of both mice and rats was comparable between groups. Peto's age-adjusted, dose-related trend analysis for the tumor-bearing rats did not reveal a statistically significant difference for males or females. There was no evidence that astemizole led to an increased incidence of spontaneously or unusually occurring neoplastic lesions in either mice or rats. Special attention was given to the effect of astemizole on the progression of spontaneously occurring mammary gland adenomas and fibroadenomas. Peto's analysis applied to the number of female rats bearing these benign mammary gland tumors disclosed no statistically significant dose-related trend. There was no positive trend for the onset of this tumor type, and the median size of the tumor over time per rat was also not statistically significantly different in a comparison of the control group with each of the dosed groups. The findings from these carcinogenicity studies suggest that astemizole is not tumorigenic and that it does not promote tumor growth.

Multicenter study with ketanserin in essential hypertension: an Argentine experiment.

One thousand eleven patients with essential hypertension (H) were evaluated upon compliance with the following inclusion criteria: (a) mild to moderate uncomplicated H, with supine diastolic blood pressure (Su DBP) greater than 90 mm Hg at the end of the placebo period, with or without antihypertensive treatment; (b) greater than 20 years old. The dosage of ketanserin (K) was 20 mg b.i.d. up to the fourth week. Afterwards, if the patients normalized, we continued with the same schedule. If this did not occur, the dosage was increased (40 mg b.i.d.) up to the eighth week. Four hundred fifty-one men and 560 women were included, with a mean age of 56.6 years, mean body weight 74.8 kg, and mean height 166.30 cm. At the end of the eighth week, the percentage of normalization was 75.5% of the patients, and the percentage of partial responders was 5.6%. The decrease of the blood pressure (diastolic and systolic) was significant at the second week (paired t test, two-tailed probability, p less than or equal to 0.001). There were 62 dropouts: 10 due to inefficacy, 14 due to adverse reaction, and 38 due to other reasons. Laboratory examinations were performed before and after treatment and did not show statistical differences. Also, a 12-lead ECG was performed before and after treatment with K. The QTc was analyzed in a sample of 140 patients and did not show statistically significant changes. The incidence of side effects was minimal (24% of the patients, n = 224), mild, and transient; only 1% of the patients dropped out due to adverse reactions. In our experience, ketanserin was an effective and safe drug, to be used primarily for the treatment of mild to moderate H.